Objective To examine the association between caregiver burden and comorbidity in elderly patients with cognitive impairment.Methods The study was conducted in 212 patients at the Memory Clinic and the Departments of Geriatrics and Neurology of Fuxing Hospital from September 2014 to September 2016.Recruited patients were assigned into a dementia group and a non-dementia group according to their cognitive status and were examined using mini mental state examination (MMSE),auditory verbal learning test (AVLT),activity of daily living (ADL),neuropsychiatric inventory(NPI),and Charlson comorbidity index(CCI).Their caregivers were surveyed with Zarit burden inventory (ZBI).Results The ZBI score was significantly correlated with patients' age,gender,CCI,MMSE,NPI,and ADL.The ZBI score was higher in male patients(21.21 ± 11.24)than in female patients(18.33±10.38).Age(r=0.10,P＜0.001),NPI(r=0.32,P＜0.001),ADL(r=0.29,P ＜0.001),and CCI(r =0.38,P ＜0.001) were positively correlated with caregiver burden,while MMSE(r =-0.28,P ＜ 0.001) was negatively correlated with it.Multiple linear regression model analysis indicated that MMSE,NPI,ADL,and CCI were influencing factors for caregiver burden.When CCI was stratified into CCIno dementia and CCIdementi8,influencing factors for caregiver burden were identified as MMSE,NPI,ADL,and CCIdementia.Conclusions Cognitive deterioration,decrease in ADL,and neuropsychiatric symptoms in elderly patients are the major causes of increased caregiver burden.Besides,the number and severity of comorbidity are independent factors for caregiver burden.

Objective To investigate the knowledge and recognition of middle aged and elderly cognitive normal people in clock drawing test (CDT) and determine the items of CDT.Methods Two hundred and sixty four middle aged and elderly cognitive normal people from community were involved in the cross-sectional study.The questionnaire was comprised of 26 items scoring in CDT in literature.Each item was rated by subjects as complete agreement, partial agreement or disagreement.Pearson correlation analysis was used to analyze the related items of age and education degree.Results There were 5 items significantly related with age and education.Twelve items enjoyed complete agreement of more than 50％ and disagreement lower than 20％.The new scoring system was composed of 12 items, including the 12 complete agreement items excepted one which was significantly related to age and education, and one item that was proved to be sensitive to cognitive impairment.Conclusion The new scoring system with 12 items for CDT may be suitable in screening cognitive impairment with high identity, and further investigation about the validity and reliability should be conducted.

Objective:To study the effect of senescence gene silent information regulator 6 (Sirt6) knockout on the brain of aged mice.Methods:Sirt6-flox transgenic mice were constructed, and the mouse brain tissue was specifically knocked out by Emx1-Cre tool mice.According to genotyping, 11 wild-type mice were selected as control group(WT group) and 10 Sirt6 gene konckout mice were selected as conditional knockout group(cKO group). Body size and body weight of the aged mice were measured and cerebral cortex thickness was measured by HE staining.Brain neurogenesis was analyzed with EdU markers.The expression of RNA-binding protein HuR and apoptosis-related protein Caspase-3 were detected by Western blot.Meanwhile, histone acetylation levels in the cortex were detected.Results:Sirt6 brain tissue-specific knocked out mice were successfully constructed.Compared with the brain tissue area((2.07±0.22) cm 2)and cortical thickness ((970.56±80.91) μm) of WT mice in the 12-month-old group, the brain tissue area ((1.61±0.14)cm 2) and cortical thickness ((822.88±53.94) μm) in Sirt6 cKO group were smaller, and the differences were statistically significant (both P<0.05). EdU incorporation into nerve cells showed that the number of EdU incorporation into periventricular nerve cells in cKO group was lower ((4.75±1.48)) than that in WT group ((10.29±1.93)). The difference was statistically significant ( P<0.001). In the experiment of 17 months age group, mice in cKO group were smaller in body size, lower in body weight ((29.00±1.08) g) and smaller in brain area ((1.54±0.55)cm 2)compared with WT group in body size, body weight ((35.25±4.17) g) and brain tissue area ((1.98±0.18) cm 2)(both P<0.05). The expression of Caspase-3 and HuR in cortical proteins of these two age groups decreased( t=2.95, 5.38, both P<0.05), and the expression of H3K9ac and H3K56ac increased( t=3.53, 2.78, both P<0.05), but the expression of Sirt1 homologous gene remained unchanged( t=1.26, P>0.05). Conclusion:The specific deletion of Sirt6 in brain tissue can lead to the decrease of brain neurogenesis in aged mice, and the aggravation of aging and the increase of apoptosis, which may be the reason for the thinning of cerebral cortex and brain tissue atrophy.The molecular mechanism is speculated to be related to the increase of acetylation level after Sirt6 knockout

Objective Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare cause of portal hypertension, and this study aims to analyze the clinical features of patients with INCPH, and to assist in diagnosis and differential diagnosis. Methods A total of 74 patients who were hospitalized in Beijing YouAn Hospital from January 2019 to July 2022 and were diagnosed with INCPH were enrolled, and 332 patients with liver cirrhosis who were hospitalized during the same period of time were enrolled as control group. Demographic data, laboratory markers, gastroscopy, liver elasticity, pathological examination, and complications were recorded and compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the ability of liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the differential diagnosis of INCPH, and the DeLong test was used to compare the area under the ROC curve (AUC). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results Among the patients with INCPH, 46.55% had no obvious symptoms at disease onset and 43.24% were misdiagnosed with liver cirrhosis. Compared with the patients with liver cirrhosis, the patients with INCPH had a significantly higher proportion of patients with gastrointestinal bleeding (62.16% vs 41.27%, χ 2 =10.67, P < 0.01) and a significantly lower proportion of patients with moderate-to-severe ascites (16.21% vs 29.82%, χ 2 =34.98, P < 0.01), and there were few patients with hepatic encephalopathy. As for pathology, 89.19% (66/74) of the INCPH patients manifested as typical occlusive portal vein disease. The statistical analysis showed that compared with the patients with liver cirrhosis, the patients with INCPH had significantly better liver function parameters, MELD score, and Child-Pugh score and significantly lower LSM [9.05(7.18-12.33) vs 25.32(16.21-47.23), Z =-8.41, P < 0.01], APRI score [0.70(0.41-1.28) vs 1.35(0.80-2.39), Z =-6.21, P < 0.01], and FIB-4 index [2.99(1.62-4.81) vs 6.68(4.06-10.42), Z =-8.39, P < 0.01]. LSM, FIB-4, and APRI had a good ability in differentiating INCPH from liver cirrhosis, and in particular, LSM had an AUC of up to 0.92 (95% confidence interval: 0.87-0.96), with a sensitivity of 92.68% and a specificity of 81.60%. Conclusion INCPH patients tend to have an insidious onset, a relatively high incidence rate of portal hypertension-related complications, and relatively good liver function, especially the patients with LSM < 14.5 kPa. The possibility of INCPH should be considered for such patients in clinical practice.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2